A Molecular Beacon Based Surface-Enhanced Raman Scattering Nanotag for Noninvasive Diagnosis of Bladder Cancer

Current techniques responsible for bladder cancer diagnosis and monitoring are insensitive and invasive. Here, we report a surface-enhanced Raman scattering nanotag for the sensitive diagnosis of bladder cancer using urine samples as a noninvasive approach. The sea-urchin-like Au nanoclusters used in this work exhibit excellent surface-enhanced Raman scattering ability with an enhancement factor of 3.44 × 10⁷. Molecular beacons labeled with Cy3 are covalently anchored to the surface of Au nanoclusters, which serve as a specific recognition site for survivin mRNA. Further a polyethylene glycol coating provides stability and completes the final functionalization. This surface-enhanced Raman scattering nanotag has good efficiency (equilibrium time: 10 min) with high sensitivity (detection threshold: 19.4 nM), high specificity (capable of single-base mismatch recognition) and good stability against nucleases. All these features are also verified in the fluorescence modality. Furthermore, its function was highly maintained in clinical samples from 13 patients with bladder cancer, as evidenced by a sensitivity up to 91.7% and a specificity up to 100%. The nanotag demonstrates its superiority over cytology and has its great clinical value even for early bladder cancer diagnosis. Thus, the nanotag is promising for noninvasive and sensitive diagnosis of bladder cancer.